2010-06-13

This article talks about the fact that scientists have largely been unable to "ferret out the genetic roots of common diseases like cancer and Alzheimer's" using the map of the human genome. Here is a typical example of what has been happening:

A medical team . . . collected 101 genetic variants that had been statistically linked to heart disease in various genome-scanning studies. But the variants turned out to have no value in forecasting disease among 19,000 women who had been followed for 12 years.

This news was not very surprising to me because I have been skeptical about theories linking diseases to genetics for a long time.

There are some diseases that are obviously genetic in origin because they follow straight Mendelian rules (Huntington's Disease, Tay-Sachs, etc.) in being passed from parents to children. However, it never made sense to me to assume a genetic component to a diseases that didn't strictly follow Mendelian rules. For example, to my way of thinking if heart disease had a significant genetic component we would expect to see clear statistically patterns of heart disease among the children of two parents who have heart disease, just like we do with Huntington's disease (and we would also expect identical twins to always both get the disease). Also, I have never heard an evidence-based explanation for why would should expect common diseases to have a genetic link. Most of the explanations I have heard have been basically "just-so" stories, along the lines of "we don't know what causes this disease so it must have a genetic origin" and/or "children of people with this disease have an increased risk for it, so it must be genetic." Neither of these arguments have ever seemed very compelling to me. Maybe diseases just happen. Maybe children are exposed to the same environmental factors as parents. Maybe there is a behavioral causes that gets passed down by parents teaching their children.

What seems odd to me is that scientists seem to be doubling down on the genetic theory of disease rather than using the recent failures of gene mapping as a wake up call that they need to be investigating new theories for the causes of these diseases:

But with most diseases, the common [genetic] variants have turned out to explain just a fraction of the genetic risk. It now seems more likely that each common disease is mostly caused by large numbers of rare variants, ones too rare to have been cataloged by the HapMap.

The underlying assumption here is that diseases must have a genetic cause, so when studies fail to find a few genetic variants causing the diseases then the theory automatically becomes that each disease must be caused by a large number of different genetic variations. But what about the possibility that these common diseases are not linked to any flavor of genetic variation? What if these diseases are exclusively caused by environmental or behavioral factors? Why discount that possibility?

I think two factors favor researchers pursuing genetic theories of disease. One is pretty obvious: if a disease is caused by genetics then it increases the probability that it can be treated with a drug, and drugs are very profitable. The other factor is that a genetic origin of disease relieves people of guilt and/or pressure to change their behavior. If a disease is caused by behavior then people with the disease tend to feel guilty about inflicting the disease on themselves, and they feel pressure to change their habits, neither of which is emotionally comfortable. The same emotional discomfort holds for diseases with environmental causes (avoiding environmental factors requires changes in behavior). Finding a genetic cause for a disease takes the social and emotional pressure off people.

Another quote from the article that I think illustrates narrow-mindedness in the scientific community:

At this point, some 850 sites on the genome, most of them near genes, have been implicated in common diseases, said Eric S. Lander, director of the Broad Institute in Cambridge, Mass., and a leader of the HapMap project. “So I feel strongly that the hypothesis has been vindicated,” he said. But most of the sites linked with diseases are not in genes — the stretches of DNA that tell the cell to make proteins — and have no known biological function, leading some geneticists to suspect that the associations are spurious.

What about the possibility that these stretches of DNA with no known biological function are controlling stuff using mechanisms we haven't even conceived of yet? What if the protein coding genes are just one small part of a vastly more complex biological control system that we haven't even imagined yet?

Towards the end the article provides support of my theory that there are complex things going on in the genome, and biology, that we haven't even begun to imagine:

But while 10 years of the genome may have produced little for medicine, the story for basic science has been quite different. Research on the genome has transformed biology, producing a steady string of surprises. First was the discovery that the number of human genes is astonishingly small compared with those of lower animals like the laboratory roundworm and fruit fly. The barely visible roundworm needs 20,000 genes that make proteins, the working parts of cells, whereas humans, apparently so much higher on the evolutionary scale, seem to have only 21,000 protein-coding genes.
The slowly emerging explanation is that humans and other animals have much the same set of protein-coding genes, but the human set is regulated in a much more complicated way, through elaborate use of DNA’s companion molecule, RNA.

If roundworms and humans have approximately the same number of genes doesn't that scream that genes are not where the interesting stuff is happening? Is anyone looking to find out what that something else is that makes the difference between humans and roundworms?

I have no idea what the answers are, but it seems to me that there are all kinds of red flags that our basic paradigm about genes, the genome, biology, and diseases are fundamentally unsound on some level and a major paradigm shifting discovery is out there waiting to be made.

The past few months I have felt that we were at risk for a double-dip recession, primarily because I don't see anything that would spark and sustain strong growth in consumer spending and without that the economy is going to be very fragile. The past few days I have been getting the feeling that the double-dip may start soon. First there was the various European debt crises. Then there was Dean Baker pointing out that mortgage applications have dropped to very low levels, which to me points to very soft housing sales in the next few months which in turn could trigger another collapse in housing prices. Then there was the stock market getting into a pattern of wild daily swings of over 1%, which to me is always a sign that a new major trend is struggling to come out of its shell (I think these daily wild swings happen when the market as a whole no longer has clear vision of what the future holds and without stable expectations for the future the market reacts strongly to daily events). Then there was the news that in April consumer income rose at a healthy pace, but consumer spending did not. And then there was the horrible jobs report yesterday showing almost no growth in employment once you net out temporary census jobs.

And then there are people like David Leonhardt at the NY Times who think the prospects for the economy are looking so rosy that it's time to start cutting government spending:

When I read stuff where people saying the future looks bright for the economy the arguments just seem weak. For example, let's look at each of the arguments made in this piece. Argument number 1:

Since the recession’s nadir, in January 2009, the job market has improved at the most rapid pace since 1983. On Friday, forecasters expect the Labor Department to report that job growth continued to accelerate in May.

He makes it sound like jobs have been growing steadily since January 2009, but if you look at this graph of total nonfarm payrolls it sure looks like jobs have only been growing since January 2010:

Couple that with Friday's report showing dismal growth outside of temporary census jobs and I don't see this as a sure sign that happy days are here again. Next argument:

Corporate executives are becoming more upbeat, surveys show. Business travel has picked up. Silicon Valley firms are doing more deals. Nissan broke ground last week on a car battery plant in Tennessee, and Chrysler is adding 1,100 jobs at a Jeep plant in Michigan.

Those are all good signs, but not really a slam dunk case for optimism. And that is it for Mr. Leonhardt's arguments for why we can stop worrying about economy and start worrying about the deficit. Convinced?